SAN DIEGO—Looking to reverse the trend of growing antibiotic resistance in pathogenic microbes, researchers at the University of California, San Diego (UCSD) announced a new program that will see them combine their expertise in pharmaceutical sciences, medicinal chemistry and oceanography to discover and develop new antimicrobials. And the initial focus of their efforts will be compounds found in ocean-dwelling microorganisms.
According to Dr. Victor Nizet, an associate professor in the Division of Infectious Diseases at UCSD's School of Medicine, the reason for the collective initiative is three-fold: urgency of need; diminished pipelines; and local capabilities.
"The magnitude of the antibiotic resistance problem in both hospital and community settings has become staggering, with great numbers of individuals afflicted and tremendous associated economic costs," he says. "Most major pharmaceutical companies have eliminated or greatly curtailed their R&D efforts in this arena and there has yet to be a major NIH initiative targeted at novel anti-infective development of sufficient scope to support a broad based discovery program.
"We recognize that UCSD by virtue of its geography and the UCSD strength of its component institutions is uniquely capable of delivering a program that takes products from their marine source of discovery, to their chemical optimization, through preclinical testing, formulation and pharmacokinetic analysis, and ultimately to early stage clinical trials," he adds.
But why the ocean? According to Nizet, terrestrial microbial resources and chemistries have been heavily mined and were essentially exhausted decades ago. Ecologists estimate the number of microbial species in the marine environment to be far greater. "Most of these marine species are still waiting to be discovered, providing a nearly unfathomable resource for potential antibiotic discoveries," he says.
UCSD is not alone in its efforts to mine the ocean for new drugs, as companies like Nereus Pharmaceuticals, PharmaMar, and Inflazyme have spent years plumbing the depths of the world's oceans to find potential therapeutics. The USCD program, however, differs in its focus on anti-infectives, as most other projects involving ocean-based microbes have looked for treatments of other conditions such as cancer or inflammation.
"Anti-infective research is a difficult and time-consuming area for drug development, and more recently, certainly during the past decade, some large pharma companies have shied away from this therapeutic class," says Kobe Sethna, Nereus president and CEO.
"However, with the increasing rate of resistance seen with current antibiotic therapy, not only in the hospital setting but also in the community setting, there is now a new focus developing in big pharma and in the biotech world to look for new anti-microbial agents. Therefore, the UCSD group is to be applauded for its new initiative because the time is absolutely right for the beginnings of a significant new program to develop new anti-infectives for the 21st century."
Nereus has a particularly close connection to—although no direct involvement in—the university's efforts as the company was co-founded by UCSD program leader Dr. William Fenical.